PNPLA3 risk allele is associated with risk of hepatocellular carcinoma but not decompensation in compensated cirrhosis.

BACKGROUND: The PNPLA3-rs738409-G, TM6SF2-rs58542926-T, and HSD17B13-rs6834314-A polymorphisms have been associated with cirrhosis, hepatic decompensation, and HCC. However, whether they remain associated with HCC and decompensation in people who already have cirrhosis remains unclear, which limits the clinical utility of genetics in risk stratification as HCC is uncommon in the absence of cirrhosis. We aimed to characterize the effects of PNPLA3, TM6SF2, and HSD17B13 genotype on hepatic decompensation, HCC, and liver-related mortality or liver transplant in patients with baseline compensated cirrhosis. METHODS: We conducted a single-center retrospective study of patients in the Michigan Genomics Initiative who underwent genotyping. The primary predictors were PNPLA3, TM6SF2, and HSD17B13 genotypes. Primary outcomes were either hepatic decompensation, HCC, or liver-related mortality/transplant. We conducted competing risk Fine-Gray analyses on our cohort. RESULTS: We identified 732 patients with baseline compensated cirrhosis. During follow-up, 50% of patients developed decompensation, 13% developed HCC, 24% underwent liver transplant, and 27% died. PNPLA3-rs738409-G genotype was associated with risk of incident HCC: adjusted subhazard hazard ratio 2.42 (1.40-4.17), p=0.0015 for PNPLA3-rs738409-GG vs. PNPLA3-rs738409-CC genotype. The 5-year cumulative incidence of HCC was higher in PNPLA3-rs738409-GG carriers than PNPLA3-rs738409-CC/-CG carriers: 15.6% (9.0%-24.0%) vs. 7.4% (5.2%-10.0%), p<0.001. PNPLA3 genotype was not associated with decompensation or the combined outcome of liver-related mortality or liver transplant. TM6SF2 and HSD17B13 genotypes were not associated with decompensation or HCC. CONCLUSIONS: The PNPLA3-rs738409-G allele is associated with an increased risk of HCC among patients with baseline compensated cirrhosis. People with cirrhosis and PNPLA3-rs738409-GG genotype may warrant more intensive HCC surveillance.

Correction: Assessing social needs among patients with cardiovascular and psychiatric comorbidities in free community health clinics.

[This corrects the article DOI: 10.1371/journal.pone.0291682.].

Assessing social needs among patients with cardiovascular and psychiatric comorbidities in free community health clinics.

BACKGROUND: Community-related health assessments have been shown to improve several outcomes in socioeconomically disadvantaged populations with comorbid chronic health conditions. However, while it is recognized that modifiable social determinant of health (SDH) factors might be responsible for up to 60% of preventable deaths, it is not yet standard of care to routinely screen and address these at preventive health appointments. The objective of this study was to identify the social needs of socioeconomically disadvantaged patients. METHODS: We performed a retrospective review of the socioeconomic screening questionnaires distributed to under- and uninsured patients seen at a medical student-run free primary care-based community clinic. This study included participants of all ages (0 and up), genders, languages, and ethnicities who filled out the social screening questionnaire. Socioeconomic screening questionnaires assessed the need for critical resources such as food, housing, utilities, finances, transportation, childcare, employment, education, legal support, companionship, health literacy, and community assistance. The primary study outcome was to identify unmet social needs of our medical student-run free clinic patients. We secondarily sought to identify associations between these needs and chronic health conditions. We hypothesized that patients with multiple chronic health problems and financial stressors would have the highest requests for resources. RESULTS: Our retrospective review identified 264 uninsured participants who were evaluated for social needs using a screening questionnaire. Participants who reported unmet social needs had significantly more cardiovascular risk factors than those who did not. Cardiovascular comorbidities and a history of psychiatric illness were the two most common medical problems significantly associated with several unmet social needs. CONCLUSION: This study provides support for the preemptive identification and appropriate management of physical, mental, and social care to improve disproportionate disparities in long-term health outcomes.

Tapered and non-tapered prosthetic grafts in upper extremity dialysis access: A systematic review and meta-analysis.

OBJECTIVE: It is unclear whether tapered arteriovenous grafts (AVGs) are superior to non-tapered AVGs when it comes to preventing upper extremity ischemic steal syndrome. We aimed to evaluate the outcomes of tapered and non-tapered AVGs using systematic review and meta-analysis. METHODS: A literature search was systemically performed to identify all English publications from 1999 to 2019 that directly compared the outcomes of upper extremity tapered and non-tapered AVGs. Outcomes evaluated were the primary patency at 1-year (number of studies (n) = 4), secondary patency at 1-year (n = 3), and risk of ischemic steal (n = 5) and infection (n = 4). Effect sizes of individual studies were pooled using random-effects model, and between-study variability was assessed using the I2 statistic. RESULTS: Of 5808 studies screened, five studies involving 4397 patients have met the inclusion criteria and included in the analysis. Meta-analyses revealed no significant difference for the risk of ischemic steal syndrome (pooled odds ratio (OR) 0.92, 95% Confidence Incidence (CI) 0.29-2.91, p = 0.89, I2 = 48%) between the tapered and non-tapered upper extremity AVG. The primary patency (OR 1.33, 95% CI 0.93-1.90, p = 0.12, I2 = 10%) and secondary patency at 1-year (OR 1.49, 95% CI 0.84-2.63, p = 0.17, I2 = 13%), and rate of infection (OR 0.62, 95% CI 0.30-1.27, p = 0.19, I2 = 29%) were also similar between the tapered and non-tapered AVG. CONCLUSIONS: The risk of ischemic steal syndrome and patency rate are comparable for upper extremity tapered and non-tapered AVGs. This meta-analysis does not support the routine use of tapered graft over non-tapered graft to prevent ischemic steal syndrome in upper extremity dialysis access. However, due to small number of studies and sample sizes as well as limited stratification of outcomes based on risk factors, future studies should take such limitations into account while designing more robust protocols to elucidate this issue.

Comparing Outcomes of Upper Extremity Brachiobasilic Arteriovenous Fistulas and Arteriovenous Grafts: A Systematic Review and Meta-Analysis.

OBJECTIVE: It is unclear what the optimal upper extremity hemodialysis access is for patients without a suitable cephalic vein for arteriovenous fistulas (AVFs). The objective of this systematic review and meta-analysis was to compare the outcomes for upper extremity transposed brachiobasilic AVFs (BBAVFs) and prosthetic arteriovenous grafts (AVGs). METHODS: A systematic review was performed to identify all English publications and abstracts comparing the patency outcomes of upper extremity BBAVFs and AVGs (January 1st, 1994 to April 1st, 2020). The outcomes assessed were 1-year and 2-year primary and secondary patency rates. Pooled odds ratios (OR) were calculated using the random-effects model, and I2 statistic was used to assess between-study variability. RESULTS: Twenty-three studies examining 2799 patients were identified and included in the study. The 1-year primary patency rates (OR = 1.68, 95% CI 1.24-2.28, p = 0.001, I2 = 69.40%) and 2-year primary patency rates (OR = 2.33, 95% CI 1.59-3.43, p < 0.001, I2 = 68.26%) were significantly better for BBAVFs than AVGs. Compared to AVGs, the 1-year secondary patency rates (OR = 1.45, 95% CI 1.05-1.98, p = 0.022, I2 = 56.64%) and 2-year secondary patency rates (OR = 1.93, 95% CI 1.39-2.68, p < 0.001, I2 = 57.61%) were also significantly higher for BBAVFs. CONCLUSION: The outcomes for upper extremity BBAVFs appear to be consistently superior to prosthetic hemodialysis access. This analysis supports the preferential placement of BBAVFs over AVGs in patients with a suitable upper extremity basilic vein.